Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma MedDRA version: 21.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Sponsors
Loxo Oncology Inc., a wholly owned subsidiary of Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 and older at time of enrollment. 2. Confirmed diagnosis by local laboratory report of CLL/SLL as defined by iwCLL 2018 criteria including the following: a) B-cells coexpressing the surface antigen CD5 together with at least one B-cell antigen (CD19, CD20, CD23) and either ? or ? light-chain restricted.In atypical cases, inclusion may be considered after discussion with the Sponsor and Sponsor approval (for CLL/SLL patients) b) = 5 × 109 B lymphocytes/L (5000/µL) in the peripheral blood (for CLL patients) c) Prolymphocytes may comprise = 55% of blood lymphocytes (for CLL patients) 3. A requirement for therapy consistent with iwCLL 2018 criteria for initiation of therapy such that at least 1 of the following should be met: a) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (such as hemoglobin 13 cm). c) Massive nodes (i.e., = 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy d) Progressive lymphocytosis with an increase of > 50% over a 2-month period, or lymphocyte doubling time < 6 months. Factors contributing to lymphocytosis other than CLL/SLL (e.g., infections, steroid administration) should be excluded e) Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids f) Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung, spine) g) Disease-related symptoms (also known as B-symptoms) as defined by any of the following: i. Unintentional weight loss = 10% within the previous 6 months. ii. Significant fatigue (i.e., Eastern Cooperative Oncology Group performance status [ECOG PS] 2 or worse; cannot work or unable to perform usual activities). iii. Fevers of 100.5°F (38.0°C) or higher for 2 or more weeks without evidence of infection. iv. Night sweats for = 1 month without evidence of infection. 4.Known 17p status (wildtype for 17p locus or positive for 17p deletion) by FISH as indicated in Section 1.2.2 5. Previously treated with at least one line of therapy that may include a covalent BTK inhibitor (patients may be eligible if they have previously received a covalent BTK inhibitor or if they have not previously received a covalent BTK inhibitor). There is no limit on prior number of lines of therapy. 6. Eastern Cooperative Oncology Group (ECOG) 0-2. 7. Must have adequate organ function, as defined in the protocol. These values must be met during the Screening Period.Results from the most recent assessment during the Screening Period will be used for eligibility. Please refer to the Protocol for the table of values. 8. Patients who have received investigational agents, anticancer treatment and/or radiotherapy are required the have the following washout periods prior to planned C1D1: a)Targeted agents: 5 half-lives or 14 days, whichever is shorter b)Cytotoxic chemotherapy: 28 days c)Anticancer therapeutic monoclonal antibodies: 28 days d)Palliative limited field radiation: 7 days e)Broad field radiation (= 30% of bone marrow or whole brain radiotherapy): 28 days 9.Prior treatment-related AEs must have recovered to Grade =1 or pretreatment baseline or are controlled with appriopriate medical treatment without meeting other exclusion criteria (with the exception of alopecia) 10.Willingness of men and WOCBP, and their pa
Exclusion criteria
Exclusion criteria: 1.Known or suspected Richter’s Transformation to diffuse large B-cell lymphoma DLBCL, prolymphocytic leukemia, or Hodgkin lymphoma at any time preceding enrollment.2.Known or suspected history of CNS involvement by CLL/SLL3.Patients who experienced a major bleeding event on a prior BTK inhibitor. Refer to Protocol for definition.4.Active second malignancy. Patients with treated second malignancy who are in remission with life expectancy > 2 years and with documented Sponsor approval are eligible. E.g. include:a) Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of diseaseb)Adequately treated cervical carcinoma in situ without current evidence of disease. c)Localized (e.g., lymph node negative) breast cancer treated with curative intent with no evidence of active disease present for more than 3 years and receiving adjuvant hormonal therapyd)Localized prostate cancer undergoing active surveillance.e)History of treated and cured Hodgkin's disease or NHL 40%d) = Grade 3 NYHA functional classification system of heart failure, uncontrolled or symptomatic arrhythmias10.Prolongation of the QTcF > 470 msec on at least 2 of 3 consecutive ECGs and mean QTcF > 470 msec on all 3 ECGs during Screeninga)QTcF is calculated using Fredericia’s Formula (QTcF = QT/(RR^0.33)b)Correction of suspected drug-induced QTcF prolongation or prolongation due to electrolyte abnormalities can be attempted at the Investigator’s discretion, and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation or electrolyte supplementationc)Correction of QTc for underlying BBB permissible11.Hepatitis B or hepatitis C testing indicating active/ongoing infection. Refer to Protocol for screening laboratory tests12. Known active CMV infection. Patients with negative status are eligible13.Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal) or other clinically significant active disease process which in the opinion of the Investigator and Medical Monitor may pose a risk for patient participation. Screening for chronic conditions is not required.14.Known HIV infection, regardless of CD4 count. Patients with unknown or negative status are eligible.15.Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (G
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate PFS of pirtobrutinib plus venetoclax and rituximab (Arm A) compared to venetoclax and rituximab (Arm B);Secondary Objective: • To evaluate the effectiveness of Arm A compared to Arm B based on overall response rate (ORR) and time to event(s) outcomes • To evaluate the safety and tolerability of each treatment arm • To evaluate the effectiveness of Arm A compared to Arm B in patient-reported disease-related symptoms and physical functioning;Primary end point(s): PFS per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018, assessed by Independent Review Committee (IRC);Timepoint(s) of evaluation of this end point: The time from the date of randomization until disease progression or death from any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Assessed by Investigator: - PFS - OS - Time to next treatment (TTNT), defined as time from the date of randomization to the date of the initiation of the subsequent anticancer therapy for CLL/SLL or death due to any cause, whichever occurs first (Section 9.4.4. for full definition). - EFS defined as the time from date of randomization to the date of disease progression (PD) or start of new treatment for CLL/SLL or discontinuation from study treatment due to toxicity or death due to any cause, whichever occurs first. • Assessed by Investigator and IRC: - ORR • Including but not limited to SAEs, AEs, deaths and clinical laboratory abnormalities per National Cancer Institute Common Terminology Criteria in Adverse Events version 5.0 (NCI CTCAE v5.0) • Time to worsening (TTW) of CLL/SLL-related symptoms • TTW of physical functioning;Timepoint(s) of evaluation of this end point: PFS - The time from the date of randomization until disease progression or death from any cause, whichever occurs first. OS- The time from randomization until death from any cause. TTNT - The time from the date of randomization to the date of the initiation of the subsequent anticancer therapy for CLL/SLL or death due to any cause, whichever occurs first EFS defined as the time from date of randomization to the date of PD, start of new treatment for CLL/SLL discontinuation from study due to toxicity or death, due to any cause, whichever occurs first. ORR - The number of patients who achieve a best overall response (BOR) of CR, CRi, nPR, or partial remission (PR) divided by the total number of patients randomized to each treatment arm. | — |
Countries
Australia, Belgium, Canada, China, Czechia, Czech Republic, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Norway, Poland, Russian Federation, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactMedical and Scientific Services
IQVIA RDS GmbH
Outcome results
None listed